Frequency and clinicopathologic associations of DNA mismatch repair protein deficiency in ampullary carcinoma: Routine testing is indicated.
Cancer
; 126(21): 4788-4799, 2020 11 01.
Article
em En
| MEDLINE
| ID: mdl-32857459
ABSTRACT
BACKGROUND:
The significance of DNA mismatch repair (MMR) deficiency in ampullary cancers (ACs) has not been established.METHODS:
In total, 127 ACs with invasive carcinomas measuring ≥3 mmthat had adequate tissue were analyzed immunohistochemically.RESULTS:
MMR loss was detected in 18% of ACs (higher than in colorectal cancers). Twelve tumors with MLH1-PMS2 loss were negative for BRAF V600E mutation, suggesting a Lynch syndrome association. MMR-deficient tumors (n = 23), comparedwith MMR-intact tumors (n = 104), showed a striking male predominance (malefemale ratio, 4.7). Although the deficient tumors had slightly larger invasion size (2.7 vs 2.1 cm), they also had more expansile growth and less invasiveness, including less perineural invasion, and they ultimately had lower tumor (T) classification and less lymph node metastasis (30% vs 53%; P = .04). More important, patients who had MMR-deficient tumors had better clinical outcomes, with a 5-year overall survival rate of 68% versus 45% (P = .03), which was even more pronounced in those who had higher Tclassification (5-year overall survival, 69% vs 34%; P = .04). MMR deficiencyhad a statistically significant association with medullary phenotype, pushing-border invasion, and tumor-infiltrating immune cells, and it occurred more frequently in ampullary-duodenal type tumors. Programed cell death-ligand 1 (PD-L1) levels analyzed in the 22 MMR-deficient ACs revealed that all medullary carcinomas were positive. Nonmedullary MMR-deficient carcinomas expressed PD-L1 in 33% of tumors cells according to the criteria for a combined positive score ≥1, but all were negative according to the tumor proportion score≥1 method.CONCLUSIONS:
In ACs, MMR deficiency is even more frequent (18%) than in colon cancer and often has a Lynch-suggestive profile, thus routine testing is warranted. Male gender, pushing-border infiltration, ampullary-duodenal origin, medullary histology, and tumor-related inflammation have a significantly higher association with MMR deficiency. MMR-deficient tumors have less aggressive behavior. PD-L1 expression is common in medullary-phenotype ACs, thus immunotherapy should be considered at least for this group.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ampola Hepatopancreática
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Neoplasias do Ducto Colédoco
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Reparo de Erro de Pareamento de DNA
Tipo de estudo:
Risk_factors_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Cancer
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Geórgia